Thomas Ryll, Ph.D., senior director, cell culture development, Biogen Idec, discussed Biogen Idec’s experience with single-use bioreactors (SUB) at the meeting.
SUB technology has advanced significantly in the last decade with many different formats now available. “We settled on a more classical design of a stirred tank based disposable reactor system,” he explained.
“A question we addressed early on was whether or not a disposable reactor system would offer sufficient mixing and mass transfer to support an intensive fed-batch culture. What I mean with intensive fed-batch culture is a culture that features high cell mass (maybe 20–40 million cells/mL) and thus requires a lot of oxygen delivery.”
Mass transfer and mixing studies conducted were positive, demonstrated equivalent blending times compared to control reactor systems, and could deliver sufficient mass transfer. “We showed that 250 L and 1,000 L SUB reactors were able to grow high cell mass and could reach high titers in the 8 g/L range,” said Dr. Ryll.
“Not every system may be able to deliver such mass transfer, and the user may want to conduct mass transfer studies and may need to tailor the system selected to the purpose in mind,” he cautioned.
A few years ago Biogen Idec also began exploring technologies for online data acquisition to better monitor and understand culture behavior. These included automated sampling and inline metabolite analysis, automated oxygen uptake rate determination, culture capacitance, and NIR and Raman spectroscopy.
Raman spectroscopy was judged to have the most potential and maturity to be developed into a real-time monitoring tool in a manufacturing environment. “We’ve been able to build models that can predict metabolite levels and cell mass online, and the idea is that this adds to our tool box in terms of culture understanding and perhaps will enable us to reduce and hopefully eliminate needs for culture sampling in the future,” said Dr. Ryll.